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研究生:施秀蘭
研究生(外文):Shih Hsiu Lan
論文名稱:葉酸濃度及相關代謝因素與女性乳癌之病例對照研究
論文名稱(外文):Associations of Folate Levels and Metabolizing Factors with Breast Cancer Risk:A Hospital-based Case-control Study
指導教授:孫建安孫建安引用關係
指導教授(外文):Sun Chien An
學位類別:碩士
校院名稱:國防醫學院
系所名稱:公共衛生學研究所
學門:醫藥衛生學門
學類:公共衛生學類
論文種類:學術論文
論文出版年:2005
畢業學年度:93
語文別:中文
論文頁數:97
中文關鍵詞:乳癌紅血球葉酸甲硫胺酸合成酶甲烯基四氫葉酸還原酶血漿同半胱胺酸
外文關鍵詞:breast cancererythrocyte folatemethionine synthase(MS)methylenetetrahydrofolate reductase(MTHFR)plasma homocysteine
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在葉酸的代謝途徑中,牽涉到甲基的轉移,當其缺乏時,會影響DNA形成、修復與甲基化,可能導致細胞癌化。而在此一過程中最主要的兩個代謝酵素:甲烯基四氫葉酸還原酶(MTHFR C677T)、甲硫胺酸合成酶(MS A2756G)之基因多形性,及反應酵素活性之中間產物同半胱胺酸濃度,皆可能與罹患乳癌風險有關。本研究為三軍總醫院所選取164名乳癌病例及322名配對對照個案進行之病例對照研究,以結構式問卷收取相關之基本變項,並利用化學冷光免疫分析紅血球葉酸濃度,酵素測定法定量血漿同半胱胺酸濃度,即時定量PCR進行MTHFR C677和MS A2756G基因型的測定,並使用邏輯式迴歸分析求得OR值及95%信賴區間。研究結果發現MTHFR為CT/TT基因型的婦女罹患乳癌的危險性較CC基因型的婦女,在停經前為0.54倍(95%信賴區間=0.31-0.95),停經後為2.23倍(95%信賴區間=1.03-4.83)。MS基因多形性及紅血球葉酸濃度與罹患乳癌危險性皆未達統計上顯著相關。而血漿同半胱胺酸濃度愈高,婦女罹患乳癌的危險性也隨之增加,且不受MTHFR C677T及MS A2756G基因多形性和停經狀態的影響。綜合言之,本研究顯示MTHFR基因多形性與罹患乳癌的危險性會受到停經狀態的影響,血漿同半胱胺酸濃度對罹患乳癌風險性為一獨立的危險因子。
Objectives : It has been known that folate metabolism is associated with DNA synthesis, repair, and methylation. A common 677C→T polymorphism in the gene of methylenetetrahydrofolate reductase(MTHFR)and 2756A→C polymorphism in the gene of methionine synthase(MS), which are the key enzymes in the metabolism of folate, have been associated with changed homocysteine levels and resultant DNA methylation, and then, in turn, could be associated with breast cancer risk. A hospital-based case-control study, including 164 breast cancer cases and 322 cancer-free matched controls, were conducted to evaluate the relationships of concentrations of folate and homocysteine as well as polymorphisms in MTHFR and MS genes with breast cancer risk.
Methods : All subjects completed an in-person interview that used a structured questionnaire. Erythrocyte levels of folate was determined by immunoassay and plasma levels of homocysteine was determined by enzymatic assay. Polymorphisms in MTHFR(C677T) and MS(A2756G) genes were determined by real-time quantitative PCR. Logistic regression models were used to compute odds ratios(ORs) and their 95% confidence intervals (CIs).
Results : There was decreased risk of breast cancer risk associated with MTHFR C677T polymorphism in premenopausal women(OR=0.54, 95% CI=0.31-0.95), whereas, an increased risk of breast cancer in relation to MTHFR C677T polymorphism was found in postmenopausal women (OR=2.23, 95% CI=1.03-4.83). However, there were no significant associations between MS A2756G polymorphism and erythrocyte folate levels with breast cancer risk. More interestingly, a significant association of plasma homocysteine levels and increased breast cancer risk was observed in this study population.
Conclusions : The association of MTHFR C677T polymorphism with breast cancer risk appeared to be modified by menopausal status. Plasma level of homocysteine was a significant independent risk factor for breast cancer in Taiwanese women.
第一章 前 言
第二章 文 獻 探 討
第一節 葉酸的代謝作用及致癌機轉
第二節 葉酸代謝酶之基因多形性
第三節 甲烯基四氫葉酸還原酶基因多形性
第四節 甲硫胺酸合成酶基因多形性
第五節 葉酸代謝酶與同半胱胺酸之關聯性
第三章 研 究 目 的
第四章 材 料 與 方 法
第一節 研究設計
第二節 研究樣本
第三節 問卷資料及生物檢體的收集
第四節 實驗方法
第五節 問卷訪視
第六節 實驗品質管制
第七節 統計分析方法
第五章 結 果
第一節 研究個案基本資料之比較分析
第二節 研究個案生活習慣之比較分析
第三節 紅血球葉酸及血漿同半胱胺酸濃度與罹患乳癌風險性之分析
第四節 MTHFR C677T及MS A2756G多形性對於罹患乳癌之易感受性
第五節 MTHFR C677T及MS A2756G基因多形性對血液葉酸及同半胱胺酸濃度之影
第六節 MTHFR C677T及MS A2756G基因多形性與血液葉酸及同半胱胺酸濃度對婦女罹患乳癌危險性之影響
第六章 討 論
第一節 MTHFR C677T基因多形性與罹患乳癌危險性之探討
第二節 MS A2756G基因多形性與罹患乳癌危險性之探討
第三節 合併MTHFR C677T及MS A2756G基因多形性對於罹患乳癌風險性之分析
第四節 紅血球葉酸及血漿同半胱胺酸濃度與罹患乳癌風險性之分析
第五節 MTHFR C677T及MS A2756G基因多形性及血液葉酸和同半胱胺酸濃度與罹患乳癌危險性之探討
第六節 研究限制
第七章 結 論 與 建 議
第八章 參 考 文 獻
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